tbuckley/cabot-search huggingface dataset:
Circumscribing Morality: The Spheres and Their Limits
Authors: Grayson R. Jackson, Jeffrey S. Farroni
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Spheres of Morality: The Ethical Codes of the Medical Profession DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Notes1 We do not deny that some patients may directly benefit from educational endeavors. Rather, we suggest that the benefits of medical education are aimed primarily at students and trainees and subsequently flow to future patients.Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Tachycardia-induced metabolic rewiring as a driver of contractile dysfunction
Authors: Chengyi Tu, Arianne Caudal, Yu Liu, Nikoloz Gorgodze, Hao Zhang, Chi Keung Lam, Yuqin Dai, Angela Zhang, Alexa Wnorowski, Matthew A. Wu, Huaxiao Yang, Oscar J. Abilez, Xuchao Lyu, Sanjiv M. Narayan, Luisa Mestroni, Matthew R. G. Taylor, Fabio A. Recchia, Joseph C. Wu
Journal: Nature Biomedical Engineering (2023)
Antigen-specific T cell responses in SARS-CoV-2 mRNA-vaccinated children
Authors: Jordan D. Philpott, Jordan Miller, Brittany P. Boribong, Saeina Charles, Jameson P. Davis, Simon Kazimierczyk, Brittany Jimena, Maureen M. Leonard, Wayne G. Shreffler, Alessio Fasano, Lael M. Yonker, Nitya Jain
Journal: Cell Reports Medicine (2023)
FDA Approval Summary: Ivosidenib in Combination with Azacitidine for Treatment of Patients with Newly Diagnosed Acute Myeloid Leukemia with an <i>IDH1</i> Mutation
Authors: Ashley Woods, Kelly J. Norsworthy, Xin Wang, Jonathon Vallejo, Edwin Chiu Yuen Chow, Ruo-Jing Li, Jielin Sun, Rosane Charlab, Xiling Jiang, Richard Pazdur, Marc R. Theoret, R. Angelo de Claro
Journal: Clinical Cancer Research (2023)

Abstract On May 25, 2022, FDA approved a supplemental application for ivosidenib (Tibsovo; Servier) extending the indication in patients with newly diagnosed IDH1-mutated acute myeloid leukemia (AML) in older adults or those with comorbidities to include the combination with azacitidine. The efficacy of ivosidenib in combination with azacitidine was evaluated in Study AG120-C-009, a phase 3, multicenter, double-blind, randomized (1:1), controlled study of ivosidenib or matched placebo in combination with azacitidine in adults with previously untreated AML with an IDH1 mutation who were 75 years or older or had comorbidities that precluded use of intensive induction chemotherapy. Efficacy was established on the basis of improved event-free survival and overall survival on the ivosidenib + azacitidine arm [HR, 0.35; 95% confidence interval (CI), 0.17–0.72; P = 0.0038, and HR, 0.44; 95% CI, 0.27–0.73; P = 0.0010], respectively. Furthermore, the rate and duration of complete remission (CR) were improved with ivosidenib versus placebo [CR 47% versus 15%, two-sided P &amp;lt; 0.0001; median duration of CR not estimable (NE; 95% CI, 13.0–NE) months versus 11.2 (95% CI, 3.2–NE) months. The safety profile of ivosidenib in combination with azacitidine was consistent with that of ivosidenib monotherapy, with important adverse reactions including differentiation syndrome (15%) and QT interval prolongation (20%).
Causal inference using observational intensive care unit data: a scoping review and recommendations for future practice
Authors: J. M. Smit, J. H. Krijthe, W. M. R. Kant, J. A. Labrecque, M. Komorowski, D. A. M. P. J. Gommers, J. van Bommel, M. J. T. Reinders, M. E. van Genderen
Journal: npj Digital Medicine (2023)
Tumor heterogeneity and immune-evasive T follicular cell lymphoma phenotypes at single-cell resolution
Authors: Sakurako Suma, Yasuhito Suehara, Manabu Fujisawa, Yoshiaki Abe, Keiichiro Hattori, Kenichi Makishima, Tatsuhiro Sakamoto, Aya Sawa, Hiroko Bando, Daisuke Kaji, Takeshi Sugio, Koji Kato, Koichi Akashi, Kosei Matsue, Joaquim Carreras, Naoya Nakamura, Ayako Suzuki, Yutaka Suzuki, Ken Ito, Hiroyuki Shiiba, Shigeru Chiba, Mamiko Sakata-Yanagimoto
Journal: Leukemia (2023)

Abstract T follicular helper (T FH ) cell lymphomas (TFHLs) are characterized by T FH -like properties and accompanied by substantial immune-cell infiltration into tumor tissues. Nevertheless, the comprehensive understanding of tumor-cell heterogeneity and immune profiles of TFHL remains elusive. To address this, we conducted single-cell transcriptomic analysis on 9 lymph node (LN) and 16 peripheral blood (PB) samples from TFHL patients. Tumor cells were divided into 5 distinct subclusters, with significant heterogeneity observed in the expression levels of T FH markers. Copy number variation (CNV) and trajectory analyses indicated that the accumulation of CNVs, together with gene mutations, may drive the clonal evolution of tumor cells towards T FH -like and cell proliferation phenotypes. Additionally, we identified a novel tumor-cell-specific marker, PLS3. Notably, we found a significant increase in exhausted CD8 + T cells with oligoclonal expansion in TFHL LNs and PB, along with distinctive immune evasion characteristics exhibited by infiltrating regulatory T, myeloid, B, and natural killer cells. Finally, in-silico and spatial cell-cell interaction analyses revealed complex networking between tumor and immune cells, driving the formation of an immunosuppressive microenvironment. These findings highlight the remarkable tumor-cell heterogeneity and immunoevasion in TFHL beyond previous expectations, suggesting potential roles in treatment resistance.
Author Correction: Thymus alterations and susceptibility to immune checkpoint inhibitor myocarditis
Authors: Charlotte Fenioux, Baptiste Abbar, Samia Boussouar, Marie Bretagne, John R. Power, Javid J. Moslehi, Paul Gougis, Damien Amelin, Agnès Dechartres, Lorenz H. Lehmann, Pierre-Yves Courand, Jennifer Cautela, Joachim Alexandre, Adrien Procureur, Antoine Rozes, Sarah Leonard-Louis, Juan Qin, Nausheen Akhter, Nazanin Aghel, Kingsley Amidi, Elizabeth Anderson, Dimitri Arangalage, Mandar Aras, Aarti Asnani, Lauren A. Baldassarre, Rocio Barovila, Ana Sofia Barroso, Wendy Bottinor, Anissa Bouali, Eve Cariou, Wei-Ting Chang, Richard K. Cheng, Shanthini M. Crusz, Anita Deswal, Pierre-Yves Dietrich, Grace Dy, Clemence Docq, Steven Ewer, Suran Fernando, Danette L. Flint, Roberta Florido, Satoshi Fukushima, Elena Galli, Elizabeth Gaughan, Manhal Habib, Andrew Haydon, Lucie Heinzerling, Osnat Itzhaki Ben Zadok, Nahema Issa, Anja Karlstaedt, Kazuo Kitagawa, Michael Layoun, Michal Laufer-Perl, Carrie Lenneman, Darryl Leong, Chloe Lesiuk, Joshua Levenson, Teresa López-Fernández, Yan Liu, Kristen Machado, Pedro Moliner, Ryota Morimoto, Michel Obeid, Anna Narezkina, Nicolas Palaskas, Giovanni Peretto, Nicolas Piriou, Juan Carlos Plana, Peter P. Rainer, Maxime Robert-Halabi, Fanny Rocher, Eugenia Rota, Francois Roubille, Theresa Ruf, Shahneen Sandhu, Francis Sanjeev, Nobuhiko Seki, Kazuko Tajiri, Yuichi Tamura, Franck Thuny, Romain Tresorier, Isik Turker, Ellen Warner, Vlad Zaha, Han Zhu, Rémi Cheynier, Benedicte Charmeteau-De Muylder, Alban Redheuil, Florence Tubach, Jacques Cadranel, Audrey Milon, Stéphane Ederhy, Thomas Similowski, Douglas B. Johnson, Ian Pizzo, Toniemarie Catalan, Olivier Benveniste, Salim S. Hayek, Yves Allenbach, Michelle Rosenzwajg, Charles Dolladille, Joe-Elie Salem
Journal: Nature Medicine (2023)
Quartet DNA reference materials and datasets for comprehensively evaluating germline variant calling performance
Authors: Luyao Ren, Xiaoke Duan, Lianhua Dong, Rui Zhang, Jingcheng Yang, Yuechen Gao, Rongxue Peng, Wanwan Hou, Yaqing Liu, Jingjing Li, Ying Yu, Naixin Zhang, Jun Shang, Fan Liang, Depeng Wang, Hui Chen, Lele Sun, Lingtong Hao, Andreas Scherer, Jessica Nordlund, Wenming Xiao, Joshua Xu, Weida Tong, Xin Hu, Peng Jia, Kai Ye, Jinming Li, Li Jin, Huixiao Hong, Jing Wang, Shaohua Fan, Xiang Fang, Yuanting Zheng, Leming Shi
Journal: Genome biology (2023)

Genomic DNA reference materials are widely recognized as essential for ensuring data quality in omics research. However, relying solely on reference datasets to evaluate the accuracy of variant calling results is incomplete, as they are limited to benchmark regions. Therefore, it is important to develop DNA reference materials that enable the assessment of variant detection performance across the entire genome.
Novel research and future prospects of artificial intelligence in cancer diagnosis and treatment
Authors: Chaoyi Zhang, Jin Xu, Rong Tang, Jianhui Yang, Wei Wang, Xianjun Yu, Si Shi
Journal: Journal of Hematology & Oncology (2023)

Research into the potential benefits of artificial intelligence for comprehending the intricate biology of cancer has grown as a result of the widespread use of deep learning and machine learning in the healthcare sector and the availability of highly specialized cancer datasets. Here, we review new artificial intelligence approaches and how they are being used in oncology. We describe how artificial intelligence might be used in the detection, prognosis, and administration of cancer treatments and introduce the use of the latest large language models such as ChatGPT in oncology clinics. We highlight artificial intelligence applications for omics data types, and we offer perspectives on how the various data types might be combined to create decision-support tools. We also evaluate the present constraints and challenges to applying artificial intelligence in precision oncology. Finally, we discuss how current challenges may be surmounted to make artificial intelligence useful in clinical settings in the future.
In early rheumatoid arthritis, anticitrullinated peptide antibodies associate with low number of affected joints and rheumatoid factor associates with systemic inflammation
Authors: Eleftheria Pertsinidou, Saedis Saevarsdottir, Vivek Anand Manivel, Lars Klareskog, Lars Alfredsson, Linda Mathsson-Alm, Monika Hansson, Martin Cornillet, Guy Serre, Rikard Holmdahl, Karl Skriner, Per-Johan Jakobsson, Helga Westerlind, Johan Askling, Johan Rönnelid
Journal: Annals of the Rheumatic Diseases (2023)

To investigate how individual rheumatoid arthritis (RA) autoantibodies associate with individual signs and symptoms at the time of RA diagnosis.
Single-cell multiomics of the human retina reveals hierarchical transcription factor collaboration in mediating cell type-specific effects of genetic variants on gene regulation
Authors: Jun Wang, Xuesen Cheng, Qingnan Liang, Leah A. Owen, Jiaxiong Lu, Yiqiao Zheng, Meng Wang, Shiming Chen, Margaret M. DeAngelis, Yumei Li, Rui Chen
Journal: Genome biology (2023)

Abstract Background Systematic characterization of how genetic variation modulates gene regulation in a cell type-specific context is essential for understanding complex traits. To address this question, we profile gene expression and chromatin accessibility in cells from healthy retinae of 20 human donors through single-cell multiomics and genomic sequencing. Results We map eQTL, caQTL, allelic-specific expression, and allelic-specific chromatin accessibility in major retinal cell types. By integrating these results, we identify and characterize regulatory elements and genetic variants effective on gene regulation in individual cell types. The majority of identified sc-eQTLs and sc-caQTLs display cell type-specific effects, while the cis-elements containing genetic variants with cell type-specific effects are often accessible in multiple cell types. Furthermore, the transcription factors whose binding sites are perturbed by genetic variants tend to have higher expression levels in the cell types where the variants exert their effects, compared to the cell types where the variants have no impact. We further validate our findings with high-throughput reporter assays. Lastly, we identify the enriched cell types, candidate causal variants and genes, and cell type-specific regulatory mechanism underlying GWAS loci. Conclusions Overall, genetic effects on gene regulation are highly context dependent. Our results suggest that cell type-dependent genetic effect is driven by precise modulation of both trans-factor expression and chromatin accessibility of cis-elements. Our findings indicate hierarchical collaboration among transcription factors plays a crucial role in mediating cell type-specific effects of genetic variants on gene regulation.
Cooperation of MLL1 and Jun in controlling H3K4me3 on enhancers in colorectal cancer
Authors: Xiang Lin, Ji-Dong Chen, Chen-Yu Wang, Zhen Cai, Rui Zhan, Chen Yang, La-Ying Zhang, Lian-Yun Li, Yong Xiao, Ming-Kai Chen, Min Wu
Journal: Genome biology (2023)
SRSF2 mutation reduces polycythemia and impairs hematopoietic progenitor functions in JAK2V617F-driven myeloproliferative neoplasm
Authors: Yue Yang, Salar Abbas, Mohammad A. Sayem, Avik Dutta, Golam Mohi
Journal: Blood Cancer Journal (2023)

SRSF2 mutations are found in association with JAK2V617F in myeloproliferative neoplasms (MPN), most frequently in myelofibrosis (MF). However, the contribution of SRSF2 mutation in JAK2V617F-driven MPN remains elusive. To investigate the consequences of SRSF2P95H and JAK2V617F mutations in MPN, we generated Cre-inducible Srsf2P95H/+Jak2V617F/+ knock-in mice. We show that co-expression of Srsf2P95H mutant reduced red blood cell, neutrophil, and platelet counts, attenuated splenomegaly but did not induce bone marrow fibrosis in Jak2V617F/+ mice. Furthermore, co-expression of Srsf2P95H diminished the competitiveness of Jak2V617F mutant hematopoietic stem/progenitor cells. We found that Srsf2P95H mutant reduced the TGF-β levels but increased the expression of S100A8 and S100A9 in Jak2V617F/+ mice. Furthermore, enforced expression of S100A9 in Jak2V617F/+ mice bone marrow significantly reduced the red blood cell, hemoglobin, and hematocrit levels. Overall, these data suggest that concurrent expression of Srsf2P95H and Jak2V617F mutants reduces erythropoiesis but does not promote the development of bone marrow fibrosis in mice.
Safety and efficacy of teclistamab in systemic immunoglobulin light chain amyloidosis
Authors: Rajshekhar Chakraborty, Divaya Bhutani, Mathew S. Maurer, Meera Mohan, Suzanne Lentzsch, Anita D’Souza
Journal: Blood Cancer Journal (2023)

Although this patient had IIIb disease based on cardiac biomarkers, the elevated cardiac biomarkers were clinically deemed to be secondary to renal failure and patient being on peritoneal dialysis (and not from advanced heart involvement).
Cellular senescence in brain aging and neurodegeneration
Authors: LS Melo dos Santos, M. Trombetta-Lima, BJL Eggen, M. Demaria
Journal: Ageing Research Reviews (2023)

Cellular senescence is a state of terminal cell cycle arrest associated with various macromolecular changes and a hypersecretory phenotype. In the brain, senescent cells naturally accumulate during aging and at sites of age-related pathologies. Here, we discuss the recent advances in understanding the accumulation of senescent cells in brain aging and disorders. Here we highlight the phenotypical heterogeneity of different senescent brain cell types, highlighting the potential importance of subtype-specific features for physiology and pathology. We provide a comprehensive overview of various senescent cell types in naturally occurring aging and the most common neurodegenerative disorders. Finally, we critically discuss the potential of adapting senotherapeutics to improve brain health and reduce pathological progression, addressing limitations and future directions for application and development.
Adjusted estimate of the prevalence of hepatitis delta virus in 25 countries and territories
Authors: D. Razavi-Shearer, H. Child, K. Razavi-Shearer, A. Voeller, H. Razavi, M. Buti, F. Tacke, N. Terrault, S. Zeuzem, Z. Abbas, A. Aghemo, U.S. Akarca, N. Al Masri, A. Alalwan, M. Alanko Blomé, A. Jerkeman, S. Aleman, H. Kamal, A. Alghamdi, M. Alghamdi, S. Alghamdi, W. Al-Hamoudi, E. Ali, A. Aljumah, I. Altraif, J. Amarsanaa, T. Asselah, O. Baatarkhuu, A. Babameto, Z. Ben-Ari, T. Berg, M. Biondi, W. Braga, C. Brandão-Mello, R. Brown, M. Brunetto, J. Cabezas, M. Cardoso, A. Martins, H.L.Y. Chan, H. Cheinquer, C.-J. Chen, H.-I. Yang, P.-J. Chen, C.-H. Chien, W.-L. Chuang, L. Cisneros Garza, B. Coco, C. Coffin, N. Coppola, M. Cornberg, A. Craxi, J. Crespo, L. Cuko, V. De Ledinghen, A.-S. Duberg, O. Etzion, M.L. Ferraz, P. Ferreira, X. Forns, G. Foster, J. Fung, G. Gaeta, J. García-Samaniego, J. Genov, L. Gheorghe, P. Gholam, R. Gish, J. Glenn, S. Hamid, J. Hercun, Y.-C. Hsu, C.-C. Hu, J.-F. Huang, R. Idilman, W. Jafri, N. Janjua, D. Jelev, J. Jia, M. Kåberg, K. Kaita, J.-H. Kao, A. Khan, D.Y. Kim, L. Kondili, M. Lagging, P. Lampertico, P. Lázaro, J.V. Lazarus, M.-H. Lee, H.-I. Yang, Y.-S. Lim, C. Lobato, G. Macedo, R. Marinho, P. Marotta, M.C. Mendes-Correa, N. Méndez-Sánchez, M.-C. Navas, Q. Ning, N. Örmeci, M. Orrego, C. Osiowy, C. Pan, M. Pessoa, Z. Piracha, C. Pop, H. Qureshi, G. Raimondo, A. Ramji, S. Ribeiro, C. Ríos-Hincapié, M. Rodríguez, W. Rosenberg, D. Roulot, S. Ryder, U. Saeed, R. Safadi, D. Shouval, F. Sanai, J.F. Sanchez-Avila, T. Santantonio, C. Sarrazin, W.-K. Seto, W.-K. Seto, M. Simonova, J. Tanaka, T. Tergast, O. Tsendsuren, C. Valente, J.M. Villalobos-Salcedo, Y. Waheed, G. Wong, V. Wong, T. Yip, V. Wong, J.-C. Wu, H.-I. Yang, M.-L. Yu, M.-F. Yuen, C. Yurdaydin, E. Zuckerman
Journal: Journal of Hepatology (2023)
Exploiting innate immunity for cancer immunotherapy
Authors: Ming Yi, Tianye Li, Mengke Niu, Qi Mei, Bin Zhao, Qian Chu, Zhijun Dai, Kongming Wu
Journal: Molecular Cancer (2023)

Abstract Immunotherapies have revolutionized the treatment paradigms of various types of cancers. However, most of these immunomodulatory strategies focus on harnessing adaptive immunity, mainly by inhibiting immunosuppressive signaling with immune checkpoint blockade, or enhancing immunostimulatory signaling with bispecific T cell engager and chimeric antigen receptor (CAR)-T cell. Although these agents have already achieved great success, only a tiny percentage of patients could benefit from immunotherapies. Actually, immunotherapy efficacy is determined by multiple components in the tumor microenvironment beyond adaptive immunity. Cells from the innate arm of the immune system, such as macrophages, dendritic cells, myeloid-derived suppressor cells, neutrophils, natural killer cells, and unconventional T cells, also participate in cancer immune evasion and surveillance. Considering that the innate arm is the cornerstone of the antitumor immune response, utilizing innate immunity provides potential therapeutic options for cancer control. Up to now, strategies exploiting innate immunity, such as agonists of stimulator of interferon genes, CAR-macrophage or -natural killer cell therapies, metabolic regulators, and novel immune checkpoint blockade, have exhibited potent antitumor activities in preclinical and clinical studies. Here, we summarize the latest insights into the potential roles of innate cells in antitumor immunity and discuss the advances in innate arm-targeted therapeutic strategies.
Determinants of fluid use and the association between volume of fluid used and effect of balanced solutions on mortality in critically ill patients: a secondary analysis of the BaSICS trial
Authors: Fernando G. Zampieri, Flavia R. Machado, Viviane C. Veiga, Luciano C. P. Azevedo, Sean M. Bagshaw, Lucas P. Damiani, Alexandre B. Cavalcanti
Journal: Intensive Care Medicine (2023)
Nuanced contribution of gut microbiome in the early brain development of mice
Authors: Xin Yi Yeo, Woo Ri Chae, Hae Ung Lee, Han-Gyu Bae, Sven Pettersson, Joanes Grandjean, Weiping Han, Sangyong Jung
Journal: Gut Microbes (2023)

The complex symbiotic relationship between the mammalian body and gut microbiome plays a critical role in the health outcomes of offspring later in life. The gut microbiome modulates virtually all physiological functions through direct or indirect interactions to maintain physiological homeostasis. Previous studies indicate a link between maternal/early-life gut microbiome, brain development, and behavioral outcomes relating to social cognition. Here we present direct evidence of the role of the gut microbiome in brain development. Through magnetic resonance imaging (MRI), we investigated the impact of the gut microbiome on brain organization and structure using germ-free (GF) mice and conventionalized mice, with the gut microbiome reintroduced after weaning. We found broad changes in brain volume in GF mice that persist despite the reintroduction of gut microbes at weaning. These data suggest a direct link between the maternal gut or early-postnatal microbe and their impact on brain developmental programming.
Modulating Gut Microbiota Prevents Anastomotic Leak to Reduce Local Implantation and Dissemination of Colorectal Cancer Cells after Surgery
Authors: Roy Hajjar, Manon Oliero, Gabriela Fragoso, Ayodeji Samuel Ajayi, Ahmed Amine Alaoui, Hervé Vennin Rendos, Annie Calvé, Thibault Cuisiniere, Claire Gerkins, Sophie Thérien, Nassima Taleb, François Dagbert, Herawaty Sebajang, Rasmy Loungnarath, Frank Schwenter, Richard Ratelle, Ramses Wassef, Eric De Broux, Carole Richard, Manuela M. Santos
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Anastomotic leak (AL) is a major complication in colorectal cancer surgery and consists of the leakage of intestinal content through a poorly healed colonic wound. Colorectal cancer recurrence after surgery is a major determinant of survival. We hypothesize that AL may allow cancer cells to escape the gut and lead to cancer recurrence and that improving anastomotic healing may prevent local implantation and metastatic dissemination of cancer cells. Experimental Design: We investigated the association between AL and postoperative outcomes in patients with colorectal cancer. Using mouse models of poor anastomotic healing, we assessed the processes of local implantation and dissemination of cancer cells. The effect of dietary supplementation with inulin and 5-aminosalicylate (5-ASA), which activate PPAR-γ in the gut, on local anastomotic tumors was assessed in mice undergoing colonic surgery. Inulin and 5-ASA were also assessed in a mouse model of liver metastasis. Results: Patients experiencing AL displayed lower overall and oncologic survival than non-AL patients. Poor anastomotic healing in mice led to larger anastomotic and peritoneal tumors. The microbiota of patients with AL displays a lower capacity to activate the antineoplastic PPAR-γ in the gut. Modulation of gut microbiota using dietary inulin and 5-ASA reinforced the gut barrier and prevented anastomotic tumors and metastatic spread in mice. Conclusions: Our findings reinforce the hypothesis that preventing AL is paramount to improving oncologic outcomes after colorectal cancer surgery. Furthermore, they pave the way toward dietary targeting of PPAR-γ as a novel way to enhance healing and diminish cancer recurrence.